Gentile Ivan, Buonomo Antonio Riccardo, Borgia Federico, Castaldo Giuseppe, Borgia Guglielmo
University of Naples "Federico II", Department of Clinical Medicine and Surgery , via S. Pansini 5, I-80131 Naples , Italy +39 081 746 3178 ; +39 081 746 3190 ;
Expert Opin Investig Drugs. 2014 Apr;23(4):561-71. doi: 10.1517/13543784.2014.892581. Epub 2014 Mar 4.
About 150,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). HCV infection can lead to liver cirrhosis, hepatocellular carcinoma and death. Treatment was based previously only on pegylated interferon combined with other antiviral drugs. Recently, the first interferon-free combination for patients with genotype 2 or 3 was approved in the USA and Europe, and several molecules are in an advanced phase of clinical development.
This review focuses on the pharmacokinetics, pharmacodynamics and tolerability of ledipasvir , an inhibitor of HCV nonstructural 5A protein. The authors also highlight the drug's safety and resistance profile.
The pharmacokinetic profile and antiviral activity of ledipasvir are ideal. However, given the high rate of natural and drug-related ledipasvir-resistant HCV mutations, ledipasvir is administered in combination regimens with other antiviral drugs, which resulted in a cure rate up to 100%. While ledipasvir is effective in patients with genotype 1 chronic hepatitis C, its efficacy remains to be established in patients with genotype 4, 5 or 6, in subjects with HIV coinfection, in hemodialyzed and elderly patients and in subjects with decompensated cirrhosis. If the excellent results of combination therapy be confirmed in larger trials, hepatologists will have the possibility to cure most HCV-positive patients in the near future.
全球约有1.5亿人慢性感染丙型肝炎病毒（HCV）。HCV感染可导致肝硬化、肝细胞癌及死亡。此前治疗仅基于聚乙二醇化干扰素联合其他抗病毒药物。最近，美国和欧洲批准了首个用于2型或3型患者的无干扰素联合疗法，且有几种药物正处于临床开发后期。
本综述聚焦于HCV非结构5A蛋白抑制剂雷迪帕韦的药代动力学、药效学及耐受性。作者还强调了该药物的安全性和耐药情况。
雷迪帕韦的药代动力学特征和抗病毒活性很理想。然而，鉴于自然产生的及与药物相关的雷迪帕韦耐药HCV突变率较高，雷迪帕韦需与其他抗病毒药物联合使用，联合治疗治愈率高达100%。虽然雷迪帕韦对1型慢性丙型肝炎患者有效，但其在4型、5型或6型患者、合并HIV感染的患者、接受血液透析的患者、老年患者以及失代偿期肝硬化患者中的疗效仍有待确定。如果联合治疗的出色结果能在更大规模试验中得到证实，肝病专家在不久的将来将有可能治愈大多数HCV阳性患者。
